Most Read Articles
Dr Margaret Shi, 18 May 2020

A blood test is shown to be feasible and safe for early detection of multiple cancers in women with no current or known history of cancer, enabling early treatment with curative intent in a subset of individuals.

Christina Lau, 12 May 2020

Patients with advanced non-small-cell lung cancer (NSCLC) who have a past medical history of pneumonitis are at increased risk of treatment-related pneumonitis (TAP) from immune checkpoint inhibitor (ICI) regimens or chemotherapy alone, an analysis of clinical trial and real-world data has shown.

Dr Margaret Shi, 14 May 2020
Pembrolizumab monotherapy improves overall survival (OS) and cancer control compared with platinum-based chemotherapy in patients with untreated locally advanced or metastatic programmed death-ligand 1 (PD-L1)–positive non-small-cell lung cancer (NSCLC) regardless of STK11 or KEAP1 mutation status, according to results of the phase III KEYNOTE-042 study. 

Rucaparib boosts PFS in BRCA-mutant recurrent ovarian cancer

Elaine Tan
21 Sep 2017

Rucaparib maintenance therapy increases progression-free survival (PFS) in BRCA-mutant recurrent ovarian cancer (OC) by 77 percent, according to late-breaking results from the ARIEL3 trial presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain.

The trial investigated PFS in 564 patients with high-grade recurrent OC (disease progression ≥6 months after penultimate platinum) who had achieved either a complete response (according to RECIST v1.1) or partial response (RECIST v1.1 or Gynecologic Cancer InterGroup CA-125 criteria) to their last platinum-based therapy. The patients were randomized in a 2:1 ratio to receive rucaparib 600 mg BID maintenance therapy or placebo. [ESMO 2017, abstract LBA40_PR]

Investigators assessed the PFS benefit of rucaparib (a PARP inhibitor with antitumour activity in BRCA-mutant OC or BRCA wild-type OC with high genomic loss of heterozygosity [LOH]) vs placebo sequentially in three groups: group 1 comprising patients with BRCA mutations (deleterious germline or somatic BRCA mutation), group 2 comprising patients with homologous recombination deficient (HRD) OC (BRCA-mutant or BRCA wild-type with high LOH), and group 3 comprising the entire intent-to-treat population.

“Results showed that compared with placebo, rucaparib led to a significant improvement in median PFS in all three groups, with the greatest improvement seen in group 1 [5.4 vs 16.6, 13.6 and 10.8 months, respectively; p<0.0001; hazard ratios, 0.23, 0.32, and 0.36, respectively],” reported lead author Professor Jonathan Ledermann of UCL Cancer Institute, London, UK.

Exploratory analyses in non-nested subgroups of patients with BRCA wild-type OC found that rucaparib treatment significantly improved PFS vs placebo. “However, as expected, a greater magnitude of PFS benefit was seen in those with high LOH [median PFS, 11.1 vs 5.6 months with placebo; p=0.0135] than those with low LOH [median PFS, 8.2 vs 5.3 months; p=0.0003],” said Ledermann.

“PFS benefit with rucaparib treatment was not dependent on time to progression since penultimate platinum therapy or whether patients had partial or complete response to their last platinum therapy,” he highlighted.

In ARIEL3, rucaparib was well tolerated with a safety profile consistent with previous phase II studies. The most common grade 3 treatment-emergent adverse events (TEAEs) associated with rucaparib were anaemia (18.8 percent vs 0.5 percent with placebo) and increase in alanine/aspartate aminotransferase levels (10.5 vs 0 percent).  “However, elevations were transient, self-limiting and not associated with other signs of liver toxicity,” Ledermann noted.

At the visit cut-off date (15 Apr 2017), 13.4 percent of patients in the rucaparib group vs 1.6 percent in the placebo group discontinued treatment due to TEAEs (excluding disease progression), and 1.6 vs 1.1 percent died due to adverse events (including disease progression).

“PARP inhibitors are the biggest development in OC therapy since the introduction of platinum drugs in the late 1970s and early 1980s. Rucaparib is clearly an exemplary member of this exciting class of drugs that can be used to treat women with recurrent OC in the maintenance setting,” Ledermann concluded.

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Most Read Articles
Dr Margaret Shi, 18 May 2020

A blood test is shown to be feasible and safe for early detection of multiple cancers in women with no current or known history of cancer, enabling early treatment with curative intent in a subset of individuals.

Christina Lau, 12 May 2020

Patients with advanced non-small-cell lung cancer (NSCLC) who have a past medical history of pneumonitis are at increased risk of treatment-related pneumonitis (TAP) from immune checkpoint inhibitor (ICI) regimens or chemotherapy alone, an analysis of clinical trial and real-world data has shown.

Dr Margaret Shi, 14 May 2020
Pembrolizumab monotherapy improves overall survival (OS) and cancer control compared with platinum-based chemotherapy in patients with untreated locally advanced or metastatic programmed death-ligand 1 (PD-L1)–positive non-small-cell lung cancer (NSCLC) regardless of STK11 or KEAP1 mutation status, according to results of the phase III KEYNOTE-042 study.